In orthopaedics, periprosthetic infection (PPI) is a devastating consequence of the insertion of implants. Currently the incidence of PPI ranges from 1 to 5%, with even greater values for high risk patients and for those that have suffered a trauma. Furthermore, about 73% of the operation reviews are carried out following a peri-implant bacterial infection. The social and economical cost of these interventions is considerably high. The etiology of PPI is complex and it depends on the ability of the bacterial species to elude the response of the host tissue, usually through the formation of a biofilm. Actually, once inserted, the implant device is coated by serum proteins. This process is followed by interactions with the cell species and the regeneration or reparation of the tissue in cases with positive course. In presence of bacterial species, the surface of the implant may be subjected to the bacterial adhesion and the formation of a biofilm. In particular, within the biofilm the bacteria are protected by the immune-surveillance system and by the effect of systemic antibiotics. In this manner, the colonization may propagate, with the harmful consequences known in the field of periprosthetic infection. A series of systems for the local release of antibiotics, both from cements and micrometric layers of biodegradable polymers deposited on the surface of the devices, were developed with the aim of fighting PPI. However, upon completing release, the porous systems of this type may serve as a protected site for the bacterial adhesion and the formation of biofilms.
Articles of literature have been recently presented in which an antibiotic, vancomycin, was covalently bonded to the surface of implant devices made of titanium and conducted bactericidal activity against bacterial species belonging to the Staphylococci genre (Chemistry & Biology, Vol. 12, 1041-1048, 2005, Vancomycin Covalently Bonded to Titanium Beads Kills Staphylococcus aureus; Journal Orthopedic Research, 25, 858-866, 2007, Vancomycin Covalently Bonded to Titanium Alloy Prevents Bacterial Colonization).
The immobilisation of vancomycin on the surface of implant devices or local release thereof are, for these applications, processes of great interest. Vancomycin constitutes a potent drug for treating Gram-positive bacterial infections, which are considerably the most common cause of periprosthetic infections. The action mechanism of vancomycin provides for the block of the synthesis of the layer of peptidoglycans of the gram-positive bacteria cell walls by means of L-Lys-D-Ala-D-Ala terminal bond of the nascent peptidoglycan. In this manner, vancomycin prevents the crosslinking which is required for the osmotic stability. The concept of firmly bonding vancomycin, per se water soluble, to the surface of the implant devices overcomes the vision of the simple release system. Actually, in this case there is a high local concentration of a drug firmly bonded to the interface between the implant device and the external environment. This stable pharmacological barrier prevents the formation of bacterial colonies on the surface of the implant device, thus preventing the occurrence of PPI. As described by Chapiro and collaborators in the article Selfprotective Smart Orthopedic Implants, Expert Rev. Med. Devices, 2007 January; 4(1):55-64, systems of this type can lead to a new generation of implant devices, which are self-protected against risks of bacterial infection due to their surface properties.
However, the process of bonding vancomycin to the surface of the device made of titanium described in these articles comprises different steps, which are quite complex from a practice point of view and not easily adaptable to industrial production, which makes it poorly suitable for devices of a given dimension and complex geometry.
Obviously, the provision, under conditions compatible with a productive context, of implant prosthetic devices capable of exploiting the pharmacological action of vancomycin would constitute a considerable step forward in the sector, with considerable scientific, social and economical implications. Ideally, the process could accompany the immobilization/release of vancomycin to provide other considerable surface properties, such as the increase of the osteointegration speed. Actually, the rapid regeneration of the bone tissue, with ensuing occupation of the available surface of the implanted device, reduces the probabilities of surface colonization by bacterial cells, completing the antibacterial protective effect due to vancomycin. This concept would allow the actual provision of devices with multifunctional surfaces, i.e. surfaces that perform, besides the obvious function of supporting the tissue components, also for example:                the function of stimulating the regeneration/reparation of the tissue        the function of antibacterial protection.        
Studies carried out by the present inventor have now revealed the possibility of practically implementing the previously mentioned concepts as described hereinafter.